Certain thiocarbamates of 2-mercaptopyridine nu-oxide and process



United States Patent CERTAIN THIOCARBAMATES 0F 2-MERCAP'I'0- PYRIDINEN-OXIDE AND PROCESS Bernard B. Brown, Hamden, Conn., assignor to OlinMathieson Chemical Corporation, a corporation of No Drawing. Filed Aug.14, 1958, Ser. No. 754,939

15 Claims. (Cl. 260-2943) This invention relates to a new group ofchemical compounds and to pesticidal compositions containing them. Moreparticularly, this invention relates to novel biologically activederivatives of Z-mercaptopyridine-l-oxide. The compounds of thisinvention are the bases and hydrohalides of the bases having theformula:

in which X is sulfur or oxygen, R is hydrogen, alkyl, alkenyl or aryl, Ris alkyl, alkenyl, aryl, alkylene or arylene and n is the valence of R.The alkyl, alkenyl and alkylene groups contain from 1 to 18 carbonatoms, inclusive. The aryl and arylene groups contain 6 to 14 carbonatoms in the aromatic nucleus and may contain alkyl or alkenylsubstituents in addition.

The 2-pyridyl-1-oxide radical, C H N( O), in the above formula and theZ-mercaptopyridine-l-oxide have the structural formulas:

H v N M -L l 0 Y O Z-pyridyl-l-oxide Z-mercnptopyridine-l-oxide I11 theformula given first above, when R is a monovalent alkyl, alkenyl or arylradical and R? ishydrogen, n is one and the compounds of this morelimited group have the formula:

C H N( O)S.C.( :X) NHR Examples of compounds of this formula include:

S-(Z-pyridyl-l-oxide) N-methyldithiocarbamate S-(Z-pyridyl-l-oxide)N-ethylmonothiocarbamate S-(Z-pyridyl-l-oxide) N-allylmonotbiocarbamateS-(2-pyridyl-1-oxide) N-i-butylmonothiocarbamate S-(Z-pyridyl-l-oxide)N-cyclohexyldithiocarbamate S-(2-pyridyl-1-oxide)N-n-octylmonothiocarbamate S-(Z-pyridyl-l-bxide) N-lauryldithiocarbamateS-(2-pyridyl-l-oxide) N-phenyldithiocarbamate S-(Z-pyridyl-l-oxide)N-naphthyldithiocarbamate S-(2-pyridyll oxide)N-p-chlorophenyldithiocarbamate In the formula first given above, when Ris an alkyl, alkenyl or aryl group and R has a valence of 1, thesubgroup of compounds of this invention has the general formula:

Examples of compounds of this type include:

S-(Z-pyridyl-l-oxide) N-dimethylmonothiocarbamate S-(Z-pyridyl-I-oxide)N-diethylmonothiocarbamate S-(2-pyridyl-1-oxide)N-diethyldithiocarbamate S-(Z-pyridyl-l-oxide)N-methyl-N-phenyldithiocarbarnate S (2 pyridyl l-oxide)N-methyl-N-allylmonothiocarbamate N-cyclopentyl-N-methyldithiocarbamate2,940,978 Patented June 14, 1960 When R in the formula first given aboveis divalent, the resulting compounds are exemplified by the following:

Di [S-(2-py1i-dyl-1-oxide)] N-ethylene bis-dithiocarbamateDi[S-(2-pyridyl-1-oxide) N-2,4-toluylene bis-monothiocarbamateThiocarbamyl halides may also he used and the Rs may be the same ordifferent alkyl, alkenyl or aryl groups. The reaction is eifected byheating the reactants in any suitable solvent and separating theproduct.

. When this method of synthesis is used, suitable salts ofZ-mercapto-pyridine-l-oxide which may be used include the sodium,potassium, ammonium, calcium and barium salts; amine salts includingtrimethylammonium and benzyldirnethylammonium salts and quaternaryammonium salts including dodecyltrirnethylammonium salts,benzylcetyldimethylammonium salts and laurylpyridinium ammonium salts.Suitable carbarnyl and thiocarbamyl halides include:

N-dimcthylcarbnmyl chloride N diethylthiocarbamyl bro- N-dlethylcarbamylchloride mide N methyl N pheuylcarbamyl Nmethyl-N-phenylthiocarbachloride myl chloride N cyclopentyl N methylcar- N cyclopentyl-N-mcthylthiobamyl chloride carbamyl chlorideN-cyclohexyl N methylcarba- N-cyclohexyl N methylthlomyl chloridecarbamyl chloride N-dimethylthiocarbamyl bromide The compounds of thepresent invention may also be prepared by reaction of salts ofmonothiocarbamic or dithiocarbamic acid with 2-ha-lopyridine-1-oxidwaccording to the following exemplary equation:

ama e Sodium dimethyl monothiocar- Sodium dimethyl dithiocarbamatebamate ,Potassium ethyl mouothiocar- Potassium ethyl dithiocarbamatebamate Sodium diethyl mouothiocar- Barium diethyl dithiocarbambamate ateDisodium ethylene bls-mono- Disodium ethylene bis-(lithiuthiocarbamatecarbamate Any 2-halopyridine-l-oxide may housed but2-chloropyridine-l-oxide or the 2-bromopyridine-l-oxide are more readilyaccessible and are therefore preferred.

Another method of preparation is the condensation ofZ-mercapto-pyridine-l-oxide with suitable isocyanates or isothiocyanatesaccording to the following equation:

In the above equation X is oxygen or sulfur and R is a monovalentradical as defined above. When an alkylene or arylene diisocyanate isused, the equation becomes:

r-inercaptopyridin'e-l-oxide andSSO cc. of benzene.

'dropsbf 'ti'iethylamine'wereadded. 36.0 grams (0.302

without employing-abasiccatalyst.

a Any of the hydrohalide salts of these .bases'can be preparedbyintroducing the appropriate hydrogen halide "gas into 'anon-aqueoussolution of the bas'e'an'd separating the preoipita'ted salt.""ihehydrochlorides -and hydrobromides are particularly preferred.

. r The compounds of this invention are ii'sefiil in dilutedcompositions as pesticides. I They actas soil fungicides, foliagefuh'gieid'es anddn the control of weeds. They are able to penetratethe'waxy coating offoliage and fruit reactions. j-However, the'reactioncan be carried out thus serve as longer lasting protective fungicidesthan, forexaniplqmetal salts of organic acids, including the heavymetalsalts of 2-'mercaptopyridirie-l'-oxide. The compounds are usedadvantageously 'in a proportion of about 15 to 80'per'centwith any'ofthe diluents usually employed for the application of foliar fungicidesor for application to the soil where they control the activity of "soilfungi. The compounds of this invention are mostly crystalline :solidsand are'suitably dispersedon *an. inert finely divided solid andemployed as a dust. Suitable solid carriers are clay, talc, bentonite,as well 'as other carriers known in 'the art. (See 'Frear, Chemistry ofInsecticides, Fungicides andHerbicidesf) Microcel'805,

'a synthetic calcium .solicate is an example of a suitable solidcarrier. The compounds may also be applied as a spray in a liquidcarrier either as a solution in asolvent or as a suspension inanon-solvent, for example, water. When applied as a suspension, suitablewetting agents and dispersants are incorporatedrMarasperse Nis asuitable f to 10 percent of thepomposition. The compounds of'thisinvention may also be admixed with carriers .that are themselves active,such asother-parasiticides,herbicides and fertilizers.

I Example I Ina flask was. placed 38.4 grams (0302 m otz- Ten mole) ofphenyl isocyanate was then added,' dropwise.

Thetemperature-rose from 19 to 33" Cnand' apreeipi- "tate formed duiingthe three-quarter hour of addition.

The reaction mixture was now heated. At 50 Call of the precipitatedissolved. However, at 60-65 C.,'another precipitate formed; After fourhours at 60-65 C., thereaction mixturewascbold andthe precipitate wasfiltered and dried. 34:6 grams of S-(2-pyridyl-1- oxide)N-phenylthiocarbanate was obtained having a melting point of 195-198 C.

Analys'is.'Calcd. for c 'rrmNgo s :s, 13.00% N,

;1 1 .3s%. FoundzS, 12.38%; N, 11.48%. 'Te'stsras'soil fungicides werecarried out by placing discs 'fof agar-c imes 5 in'diameter of thepatho- 'thiocarbainate. The plates were then incubatedfor 48 hours at C.to giv' l atisfactofy*growthbt'the fiingi on control platescontaining nochemical. The growth ofthe fungi on the test-plates was then-observedanddescribed-as 0 for no growth, indicating a kill of the fungi, or'+indicating no. inhibition of fungal growth andytherefore, nopronounced depressing effect-of the chemical being tested. The followingresults were ain The above 'fesnlts indicate thatrthis ifcdmpound insuitable concentration controls the growth of each of the aboveorganisms.

' a Example-II 2=chloropyridine-loxide (-0.40 mole).-dissolved-invmlxofmethanol was heated] to refluxing. Aisolution of 0.20 rnole'o f'disodium ethylene bis-dithiocarbamate in ;--250 ml. ;ofmethanol; wasadded over-a .period-of -l .5 hours. At -the;end =of'the reaction.period, the sodium chloride formed was removed by filtration and thefiltrate was concentratedtoyield crude d'i'[S-(2-pyridyl-1- oxide)]N-ethylene bis -dithiocarbamate. After crystallizing from methanol,the'pure ,-1n'aterial 'melted at -14-3.5144.5 C. and analyzed 13.25percent nitrogen compared with a theoretical -valne of 14.-1.percent.

Example III 2-chloropyridine-'1 bxide (0.'40 mole) was dissolved in 150ml. of=methanoll and'lieatedtorefluxifig. 'A sollition of 0.20 'mole ofdisodium ethylene ibis-dithiocarbamate in 250 ml. of methanol wasaddedfoverfiaiperiod ofvlfi hours. At the end of the reaction period,the sodium chloride formed was removed by filtration and the filtratewas concentrated to yield 35 grams 44 percent) of diES- (2 pyridyl 1-oxid'e) N-ethylenebis dithiocarbamate melting at 126-130 C. Tworecrystallizations from methanol gave 22.0 -grams of pure materialhaving a melting point of 142-1425 -C. This was-identical with theproduct of Example II. r

{Foliage-fungicide -tests, rperforme'd as described in ffBhytopathology,3-3, 6279632 l 1943 37, 354 -356 (1947), showed that a concentration of25;.p.p.1:n. of--the- 'stirred "in; water, "this 'composition'formed .a

'f stable suspension lwasisuitabl'e for application by "spraying'togrowing" plants.

precipitate formed during the 45 minute addition. The

. precipitate was removed by filtration and dried. .The-' i2.5

grains'of precipitate We're" purified by 'siurrying with acetone,filtering and drying to give 32.2 grams of product identified asS-(Z-pyfldyl-l-oxide) N-p-chlorophneylthiocarbamate having a meltingpoint of 198-l99.5 C. Analysis-Cale. fOI' c zHgNzozscli S, Found: S,10.88%.

Example V In a flask was placedl0.1 grams (0.078 mole) of 2-chloropyridine-l-oxide in 50 ml. of ethanol. 13.4 grams of sodiumdiethyldithiocarbamate (0.078 mole) was dissolved in 200 ml. of ethanoland added to the refluxing 2-chloropyridine-l-oxide solution over aperiod of 1.5 hours. The mixture was refluxed 33 hours by which 58percent of the theoretical by-product sodium chloride was recovered onfiltration. The filtrate was concentrated to an oil which would notcrystallize on billing or scratcll ng. This oil was dissolved in benzeneand hydrogen chloride was passed into the solution until precipitationno longer occurred. The precipitated hydrochloride liquefied on standingbut crystallized on chilling to a product melting at 135-l50 C. Theprodnot was purified by dissolving in ethanol and precipitating byaddition of n-hexane to give 5.1 grams of material melting at 142-145"C. identified as S-(Z-pyridyll-oxide) N-diethyldithiocarbamatedihydrochloride.

Analysis.Calc. for C H N OS Cl N, 8.88%; CI, 28.27%. Found: N, 3.76%;Cl, 26.34%.

Example V! In a flask was placed 19.2 grams (0.15 mole) of 2-mercaptopyridine-l-oxide in 250 ml. of benzene. 15.2 grams (0.15 mole)of triethylarnine was added. 20.3 grams (0.15 mole) of N-diethylcarbarnyl chloride was added dropwise to the refluxing solution over aperiod of 0.25 hour. The mixture was refluxed 0.75 hour longer, cooledand the precipitate of by-product triethylamine hydrochloride wasremoved by filtration. Hydrogen chloride gas was passed into thefiltrate to yield 13.0 grams of producthaving a melting point of 104-15C. Recrystallization from ethanol yielded 3.5 grams of product meltingat 122-40" C. which was identified by infra red spectra and analysed asS-(Z-pyridyl-l-oxide) N- diethylmonothiocarbamate dihydrochloride.

Analysis.-Calc. for C l-l N O Scl N, 9.42%; Cl, 23.69%. Found: N, 8.17%;Cl, 23.02%.

Example VII To a solution or" 19.7 grams (0.155 mole) ofZ-mercaptopyridinel-oxide in 130 cc. of benzene there was addeddropwise, r42 grams (0.0817 mole) of toluylene diisocyanate, acommercial mixture of about 80 percent of 2,4-toluylene diisocyanate and20 percent of 2,6-toluylene diisocyanate. The temperature rose from 24to 30 C. during the addition. Thereafer, the mixture was heated to 55 C.for two hours and cooled. The precipitate which formed was filtered anddried. The yield was 12.3 grams of product melting above 300 C.

Foilage tests performed as described in Phytopathology 33, 627-632(1943); 37, 354-356 (1947), showed that a concentration of 25 parts permillion of the product of this example completely inhibited thegermination of the spores of Monolinia fructicola, an organism whichcauses brown rot of stone fruit.

Example VH1 In a flask was placed a solution of 33.1 grams (0.3 mole) ofZ-mercaptopyridine-l-oxide in 220 cc. of benzene. To it was added asolution or" 29.7 grams (0.3 mole) of allyl isothiocyanate in 50 cc. ofbenzene. The mixture was heated to 50-60 C. for four hours. It remaineda clear solution. The benzene was distilled at 40 C./ 170 mm. and theunreacted allyl isothiocyanate was distilled at 34 C./l5 mm. Theresidual product distilled at 81-91 C./C'.4 mm. solidified upon cooling,MP. 6078 C.

Foliage fungicide tests performed as described in Phytopathology 33,627-632 (1943); 7, 354-356 (1947), showed that a concentration of 25parts per million of the product of this example completely inhibitedthe germination of the spores of Zl Ionolinia fructicola, an organismwhich causes brown rot of stone fruit.

I claim:

1. A compound selected from the group consisting of tree bases andhydrochlorides of free bases having the formula:

in which X is selected from the group consisting of sulfur and oxygen, Ris selected from the group consisting of alkyl, alkenyl, alkylene,monocyclic aryl hydrocarbon, arylene hydrocarbon and cycloallrylContaining 1 to 18 carbon atoms, R is selected from the group consistingof hydrogen and alkyl, alkenyl, monocyclic aryl hydrocarbon andcycioalkyl containing 1 to 18 carbon atoms and n is the valence of R.

2. S-(Z-pyridyl-l-oxide) N-phenylmonothiocarbamate.

3. S-(2-pyridyl-l-oxide) N-diethyldithiocarbamate.

4. Di-/S-(2-pyridyl-1-oxide)/N-ethylene bis-dithiocatbamate.

5. Di-/S-(Z-pyridyl-l-oxide) /N-p-chlorophenyl monothiocarbamate.

6. A process for the preparation of a compound according to claim 1which comprises reacting 2-mercaptopyridine-l-oxide with a compound ofthe formula X:\./-N in which R and X are defined as in claim 1.

7. A process according to claim 6 in which the reaction is carried outin the presence of a basic catalyst.

8. A process for the preparation of S-(Z-pyridyl-loxide)N-phenylthiocarbamate which comprises reactingZ-mercaptopyridine-l-oxide with phenylisocyanate and recovering thereaction product.

9. A process according to claim *8 in which the reaction is carried outin the presence of triethylamine.

10. A process for the preparation of a compound according to claim 1which comprises reacting a salt of Z-rnercaptopyridine-l-oxide with acarbamyl halide.

11. A process according to claim 10 in which the reaction is carried outin the presence of a basic catalyst.

12. A process for the preparation of S-(Z-pyridyl-loxide) Ndiethylmonothiocarbamatedihydrochloride which compiises reactingZ-mercaptopyridine-l-oxide with N-diethylcarbamyl chloride, introducinghydrogen chloride and recovering the reaction product.

13. A process according to claim 12 in which the reaction is carried outin the presence of triethylamine.

14. A process for the preparation of a compound according to claim 1which comprises reacting a 2-halopyridine-l-oxide with a salt of an acidselected from the group consisting of thiocarbamic acid anddithiocarbamic acid.

15. A process for the preparation of diES-(Z-pyridyll-0xide)l N-ethylenebis-dithiocarbamate which comprises reacting 2-chloropyridine-1-oxidewith disodium ethylene bis-dithiocarbamate and recovering the reactionproduct.

' References Cited in the file of this patent UNITED STATES PATENTS2,621,143 Goodhue et a1. Dec. 9, 1952 2,681,879 Gysin et al. June 22,1952 2,686,786 Shaw et a1. Aug. 17, 1954

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF FREE BASES ANDHYDROCHLORIDES OF FREE BASES HAVING THE FORMULA: